Glutathione is present in almost all biological tissues as a major intracellular reducing agent and plays important roles in catalysis, metabolism, transport and protection of cells. To be particular as to the protection of cells, glutathione displays said function (1) by reductively destorying reactive oxygen compounds and free radicals with the acid of glutathione peroxidase or (2) by reacting with intracellular toxic compound with the aid of glutathione-S-transferase and the reaction product being excreted out of the cells as a glutathione conjugate, thus playing roles in antioxidation, detoxication, protection against radiation injury, and increasing resistance to temperature, etc.
Therefore, when the tissue content of glutathione has decreased due to diseases or aging, the tissue becomes liable to suffer injuries. It is important for the restoration of lost cellular functions to decreased tissue glutathione levels to the normal value and it is also generally regarded that the cellular protective function can be further enhanced by increasing the tissue glutathione even in case of a normal cell. Actually it has also been reported that glutathione and several kinds of thiol compounds were used effective in protecting against mutagenic and carcinogenic substances and further in reducing the tumor size of the animal liver caused by from said malignant substances.
However, there are problems that half life of glutathione in blood is short (several minutes) and administration of glutathione itself is not so useful in increasing tisse glutathione. It is considered that this is due to the facts that glutathione itself can not be taken efficiently into cells, and exogenously supplied glutathione must be once degraded to its constituent peptide or amino acids, which are able to be transported and converted intracellularly to glutathione.
There have been several compounds that overcome problems above-mentioned and are proved to be superior to glutathione in increasing glutathione level of human lymphoma cells or animal tissues. 2-oxothiazolidine-4-carboxylate, .gamma.-L-glutamyl-L-cysteine, and r-L-glutamyl-L-cysteinyl-glycine ethyl ester (glutathione monoethyl ester), etc. (for instance, Curr. Top. Cell. Regul., vol. 26, pp 383-394, 1985; Fed. Proc., vol. 43, pp 3031-3043, 1984).